Sustained-release narcotic drugs are highly sought after by drug abusers because they provide a much more powerful euphoric high than immediate-release formulations. Drug abusers easily defeat the sustained-release feature then ingest, snort or inject the narcotic drug for an immediate and potent drug high. The abuse of oxycodone (Purdue Pharma's "OxyContin(tm)") and the resulting risk to public health and safety has been highly publicized in recent years. In 2005, Purdue Pharma plans to launch sustained-release hydromorphone, a more potent narcotic than oxycodone. This new, sustained-release hydromorphone product is expected to have the same abuse vulnerabilities as OxyContin tablets. These abuse vulnerabilities, combined with the greater potency of hydromorphone compared to oxycodone, may create a potential public health risk from narcotic abuse of a magnitude that could exceed that of OxyContin. In this application, Pain Therapeutics, Inc. proposes initial formulation work for an abuse-deterrent sustained-release hydromorphone product that will be based upon a patented, sustained-release oral dosage form technology. Pain Therapeutics, Inc. is currently developing a similar abuse-deterrent sustained-release formulation of oxycodone, which is in Phase I clinical trials. This formulation is highly resistant to abuse as it cannot be crushed, and its 12-hour oxycodone dose cannot be extracted in common beverages including alcohol. The aim of this proposal is to use the same technology to develop a sustained-release hydromorphone formulation that similarly resists abuse yet will provide long-acting pain relief. [unreadable] [unreadable]